Thursday, June 13, 2019

BTK-Inhibitors at the 2019 EULAR Meeting in Madrid

Again there is a hype on small molecules as JAK-inhibitors are on the market and the drug are sold at exorbitant prices – for a small, less complex molecules as compared to large, complex molecules like MABs with much higher production costs. So it is understandable that companies try to come to the market with such drugs. Filgotinib is presented in 10 studies at the 2019 EULAR Meeting in Madrid; as tofacitinib and as baricitinib.

Bruton’s tyrosine kinase (BTK) plays an essential role in B cell development and is thought to be involved in the pathogenesis of RA. There are 5 studies on different BTK-inhibitors at the 2019 EULAR Meeting.

I’ve had a discussion on twitter with friend and colleague Dr Irwin Lim (@_connectedcare) on Twitter yesterday [1]. So I looked deeper into BTK-inhibitors.

Acalabrutinib (Calquence®)
Acalabrutinib (Calquence®) by AstraZeneca: study completed, but no published data on outcome (DAS28) in April 2015. Nothing at the 2019 EULAR Meeting. Calquence® has been approved by the FDA and the EMA for the treatment of mantle cell lymphoma (MCL).

AC0058 by ACEA has an ungoing study on systemic lupus erythematodes (NCT03878303), which is still recruiting. I haven't found a study on rheumatoid arthritis.

BMS-986142 by Bristol-Myers Squibb: study completed, but no published data on outcome (ACR20, ACR70) in Feb. 2016. Nothing at the 2019 EULAR Meeting.

Evobrutinib by Merck: study ongoing (ACR20) in Jul. 2017. Nothing at the 2019 EULAR Meeting.

Fenebrutinib by Roche/Genentech: study completed (ACR50) in Sep. 2016. There are two studies. St. Cohen and colleagues concluded in phase 2 study: “FEN [Fenebrutinib] demonstrated higher efficacy rates than PBO [placebo] for ACR50 at W12 in both MTX-IR and TNF-IR [inadequate response] populations, and was similar to ADA [adalimumab] in MTX-IR pts. The overall safety profile of FEN was acceptable.“ [2] The other study is a cell study (THE BTK INHIBITOR, FENEBRUTINIB, EFFECTIVELY MODULATES B AND MYELOID CELL BIOLOGY IN RHEUMATOID ARTHRITIS PATIENTS).

Poseltinib (LY3337641) by Eli Lilly: study terminated because of lack of efficacy (ACR20) in Aug. 2016. Early in 2018 Eli Lilly has halted a phase 2 trial on rheumatoid arthritis after looking at the mid-study data. Probably the efficacy goal wasn’t likely to be met (ACR20). [3] These study results will be discussed at the 2019 EULAR Meeting on Saturday.

Spebrutinib by Celgene failed to meet primary outcome (ACR20) in Oct. 2013. Nothing at the 2019 EULAR Meeting.

TAS 5315
TAS 5315 is a BTK inhibitor by Taiho. There are two animal studies at the 2019 EULAR Meeting.

Tirabrutinib (ONO-4059) by Ono Pharmaceutical/Gilead Sciences: there had been some efficacy in a CIA study, but nothing more than a phase 1 study for rheumatoid arthritis so far.

Irwin, you’ve written: Fenebrutinib in RA - some promise #eular2019, and I have to admit, I come to the same conclusion. I had answered: BTK inhibitor? There have been posters for a long time. Is the small molecule hype back? #EULAR2019 #Fenebrutinib. There is some promise as fenebrutinib showed a similar response like adalimumab. Now, we’ll have to wait for a phase 3 study and of course the approval by FDA, EMA and other countries’ boards. Hopefully, the price level will be lower than it is now with other small molecules.

[2] St. Cohen and colleagues: Ann Rheum Dis, volume 78, supplement 2, year 2019, page A80


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